obesity: epidemiology, pathophisiology and clinical picture carruba.pdf · obesity: epidemiology,...

38
Department of Biotechnology and Traslational Medicine CENTER FOR STUDY AND RESEARCH ON OBESITY University of Milan, Italy OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba Department of Medical Biotechnology and Traslational Medicine University of Milan Via Vanvitelli, 32 20129 Milan (Italy)

Upload: truongthuan

Post on 19-Jan-2019

221 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Department of Biotechnology and Traslational

Medicine

CENTER FOR STUDY AND RESEARCH ON OBESITY

University of Milan, Italy

OBESITY:

EPIDEMIOLOGY,

PATHOPHISIOLOGY

AND CLINICAL PICTURE Michele O. Carruba

Department of Medical

Biotechnology and Traslational

Medicine

University of Milan

Via Vanvitelli, 32

20129 – Milan (Italy)

Page 2: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

L’evoluzione della specie

Page 3: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

IL BILANCIO ENERGETICO

Centro Studio e Ricerca sull’Obesità (C.S.R.O.)

Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica,

Università degli Studi di Milano, Via Vanvitelli 32, Milano

Prof. Michele Carruba

Page 4: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Prevalence of Obesity and Diagnosed

Diabetes Among US Adults, 1991 and 2001

Page 5: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Distribuzione della popolazione italiana nelle varie

condizioni di peso

Sottopeso

Normopeso

Sovrappeso

Obeso

4.000.000

16.000.000

1.500.000

Fonte: ISTAT, 4° Rapporto sull’Obesità in Italia. Istituto Auxologico Italiano, 2002

Page 6: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 7: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 8: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Prevalenza dell’obesità (IMC>30) in funzione dell’età negli

UOMINI

0

2

4

6

8

10

12

14

16

18-24 25-34 35-44 45-54 55-64 65-74 >74

%

Fonte: ISTAT, 4° Rapporto sull’Obesità in Italia. Istituto Auxologico Italiano, 2002

Page 9: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Prevalenza dell’obesità (IMC>30) in funzione dell’età nelle

DONNE

0

2

4

6

8

10

12

14

16

18-24 25-34 35-44 45-54 55-64 65-74 >74

%

Fonte: ISTAT, 4° Rapporto sull’Obesità in Italia. Istituto Auxologico Italiano, 2002

Page 10: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Sovrappeso e obesità aumentano il rischio

di MCV e di mortalità per tutte le cause

Dati relativi a 1 milione di uomini e donne seguiti per 16 anni con età media di 57 anni che non hanno mai fumato e non avevano una storia di malattia all’arruolamento.

Calle et al. N Engl J Med. 1999;341:1097-1105

Ris

ch

io r

ela

tivo

di

mo

rta

lità

pe

r tu

tte

le

ca

use

Mortalità per tutte le cause

Ris

ch

io r

ela

tivo

di

mo

rta

lità

pe

r m

ala

ttia

ca

rdio

va

sco

lare

Mortalità per MCV

0.6

3.0

2.6

2.2

1.8

1.4

1.0

>18 25 30 >40 BMI (kg/m2)

Donne Uomini

Normopeso Obesi Sovrappeso

BMI (kg/m2) 0.6

3.0

2.6

2.2

1.8

1.4

1.0 Normopeso Obesi

Donne Uomini

sovrappeso

>18 25 30 >40

Page 11: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Peeters et al. Ann Intern Med 2003; 138: 24-32

35

40

45

50

Donne Non-fumatrici Uomini Non-fumatori

Aspettativa di vita a 40 anni di età Normali (18,5-24,9 kg/m2)

Sovrappeso (25-29,9 kg/m2)

Obesi (30 kg/m2)

46.3

43.0

39.2

43.4

40.3

37.5

7,1 anni

5,8 anni

3,1 anni

3,3 anni

Aspettativa di vita a 40 anni: impatto

dell’eccesso di peso corporeo

Page 12: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Years of life lost and healthy life-years lost from

diabetes and

cardiovascular disease in overweight and obese

people:

a modelling study SA Grover et al. Lancet Diabetes Endocrinol. Published online December 5, 2014

Page 13: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 14: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 15: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Un parametro fondamentale: la

circonferenza addominale

Page 16: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 17: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Unmet clinical need associated with

abdominal obesity

Patients with

abdominal obesity

(high waist

circumference) often

present with one or

more additional

CV risk factors

NHANES 1999–2000 cohort (data on file)

CV risk factors in a typical patient with abdominal obesity

Page 18: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Adverse cardiometabolic effects of

products of adipocytes

Adipose

tissue

↑ IL-6

↓ Adiponectin

↑ Leptin

↑ TNFα

↑ Adipsin

(Complement D)

↑ Plasminogen

activator inhibitor-1

(PAI-1)

↑ Resistin

↑ FFA

↑ Insulin

↑ Angiotensinogen

↑ Lipoprotein lipase

↑ Lactate

Inflammation

Type

2 diabetes

Hypertension

Atherogenic

dyslipidaemia

Thrombosis Atherosclerosis

Lyon 2003; Trayhurn et al 2004; Eckel et al 2005

Page 19: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Overweight, Obesity, and Mortality from Cancer in a

Prospectively Studied Cohort of U.S. Adults

Eugenia E. Calle, Ph.D., Carmen Rodriguez, M.D., M.P.H.,

Kimberly Walker-Thurmond, B.A., and Michael J. Thun, M.D.

The New England Journal of Medicine, 348: 1625-1638, 2003

The heaviest members of this cohort (body-mass index of at least 40) had death rates

from all cancers combined that were 52 percent higher (for men) and 62 percent

higher (for women) than the rates in men and women of normal weight.

In both men and women, body-mass index was also significantly associated with

higher rates of death due to cancer of the esophagus, colon and rectum, liver,

gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's

lymphoma and multiple myeloma. Significant trends of increasing risk with higher

body-mass-index values were observed for death from cancers of the stomach and

prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in

women.

Conclusions. Increased body weight was associated with increased death rates for all

cancers combined and for cancers at multiple specific sites.

Page 20: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Abdominal obesity increases the

risk of developing type 2 diabetes

<71 71–75.9 76–81 81.1–86 86.1–91 91.1–96.3 >96.3

24

20

16

12

8

4

0

Rela

tive r

isk

Waist circumference (cm)

Carey et al 1997

Page 21: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Intra-abdominal adiposity and

dyslipidaemia

Pouliot et al 1992

310

248

186

124

62

0

60

45

30 m

g/d

L

mg

/dL

Triglycerides

Lean

HDL-cholesterol

Visceral fat

(obese subjects)

Low High Lean

Visceral fat

(obese subjects)

Low High

Page 22: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Abdominal obesity and

increased risk of CHD Waist circumference was independently associated with

increased age-adjusted risk of CHD, even after adjusting for

BMI and other CV risk factors

0.0

0.5

1.0

1.5

2.0

2.5

3.0

<69.8 69.8-<74.2 74.2-<79.2 79.2-<86.3 86.3-<139.7

1.27

2.06 2.31

2.44 p for trend = 0.007

Rela

tive r

isk

Rexrode et al 1998

Quintiles of waist circumference (cm)

Page 23: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Abdominal obesity and increased

risk of cardiovascular events

Dagenais et al 2005

Ad

juste

d r

ela

tive r

isk

1 1 1

1.17 1.16 1.14

1.29 1.27

1.35

0.8

1

1.2

1.4

CVD death MI All-cause deaths

Tertile 1

Tertile 2 Tertile 3

Men Women <95

95–103 >103

<87

87–98 >98

Waist

circ. (cm):

Adjusted for BMI, age, smoking, sex, CVD, disease, DM, HDL-C, total-C

The HOPE Study

Page 24: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 25: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 26: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Elaborazione Centro Studi Ricerca Obesità (CSRO) e

Farmacoeconomia UniMI

“STUDIO SPESA” : COSTI DIRETTI

ANNUI DELL’OBESITÀ IN ITALIA

Nel 2025 costo Tot (mld) da 11 a 15,7 (+43%) con obesità infantile + 205%

Studio SPESA: composizione dei costi

dell’Obesità Tot 28,2 mld Euro/anno

Voce di costo Percentuale

Ospedalizzazioni 64%

Diagnostica 12%

Farmaci 7%

Visite 6%

Altro 11%

Centro Studio e Ricerca sull’Obesità (C.S.R.O.)

Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica,

Università degli Studi di Milano, Via Vanvitelli 32, Milano

Prof. Michele Carruba

Page 27: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 28: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Science 299: 896-899, 2003

Page 29: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

NA

eNOS

Other

signals

cAMP

Proteins for mitochondrial

biogenesis and function

UCP1

UCP1

UCP1

b3AR

Brown adipocyte

Heat

Cold is sensed

by the brain

Sympathetic nerves are activated

NO cGMP

PGC-1

cGMP NO

eNOS

? ?

? Nucleus

Mitochondrion

Lipid droplets

Page 30: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Electron microscopy analysis of WAT, BAT and muscle in

ob/ob mice

WAT

Valerio et al., J. Clin. Invest., Oct. 2006

Page 31: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

45

5

40

35

30

25

20

15

10

0

45

5

40

35

30

25

20

15

10

0 4 8 12 16 20 24 28 32 36 40 44 48 52 4 8 12 16 20 24 28 32 36 40 44 48 52

Body w

eig

ht

(g)

Bod

y w

eig

ht

(g)

Males Females

Time (weeks) Time (weeks)

a b

Growth curves of wild-type and eNOS-/- mice

wt

eNOS -/- wt

eNOS -/-

Nisoli et al., Science 299, 896–899, 2003

Page 32: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Visceral fat depot in eNOS-/- vs. wild-

type mice

wt eNOS-/-

Page 33: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Decreased energy levels can

cause and sustain obesity

Food

Fuel

ATP = Energy

Fat

Food

Fuel

ATP = Energy

Fat

Healthy subject Obese subject

Page 34: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Food

Fuel

ATP = Energy

Fat

Low ATP

in cells

Brain

Leptin

Page 35: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Sience October 14, 2005

Centro Studio e Ricerca sull’Obesità (C.S.R.O.)

Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica,

Università degli Studi di Milano, Via Vanvitelli 32, Milano

Prof. Michele Carruba

Page 36: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Several weeks of intense endurance

training enhances mitochondrial

biogenesis in humans.

J Appl Physiol 99: 1372–1377, 2005

Centro Studio e Ricerca sull’Obesità (C.S.R.O.)

Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica,

Università degli Studi di Milano, Via Vanvitelli 32, Milano

Prof. Michele Carruba

Page 37: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral
Page 38: OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Michele O. Carruba ... 896–899, 2003 . Visceral

Integrated Laboratories Network (InLaNe)

Center for Study and Research on

Obesity, University of Milan (Italy)

Enzo Nisoli, M.D. Ph.D.

Laura Tedesco, Ph.D.

Maurizio Ragni, Ph.D.

Renata Bracale, Ph.D.

Andrea Fossati, Ph.D.

Annalisa Cardile, Ph.D.

Chiara Ruocco, Ph.D.

Michele O. Carruba, M.D. Ph.D.

Department of Medicine,

University of Padua,

Padua

(Italy) Roberto Vettor, M.D.

Elisabetta Trevellin, Ph.D.

Marnie Granzotto, Ph.D.

Massimiliano Olivieri, Ph.D.

Roberto Fabris, M.D.

Roberto Serra, M.D.

Department of Biomedical

Sciences and Biotechnology,

University of Brescia,

Brescia

(Italy)

Alessandra Valerio, M.D. Ph.D.

Fracesca Fenaroli, Ph.D.

Mattia Bicelli, Ph.D.